A nonhuman primate model of vertical sleeve gastrectomy facilitates mechanistic and translational research in human obesity

The obesity epidemic significantly contributes to overall morbidity and mortality. Bariatric surgery is the gold standard treatment for obesity and metabolic dysfunction, yet the mechanisms by which it exerts metabolic benefit remain unclear. Here, we demonstrate a model of vertical sleeve gastrecto...

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Published iniScience Vol. 24; no. 12; p. 103421
Main Authors Nugent, Julia L., Singh, Amar, Wirth, Keith M., Oppler, Scott Hunter, Hocum Stone, Laura, Janecek, Jody L., Sheka, Adam C., Kizy, Scott, Moore, Meghan E.G., Staley, Christopher, Hering, Bernhard J., Ramachandran, Sabarinathan, Ikramuddin, Sayeed, Graham, Melanie L.
Format Journal Article
LanguageEnglish
Published Elsevier Inc 17.12.2021
Elsevier
Subjects
Immunology
Obesity medicine
Surgery
Obesity medicine
Surgery
Immunology
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Summary:The obesity epidemic significantly contributes to overall morbidity and mortality. Bariatric surgery is the gold standard treatment for obesity and metabolic dysfunction, yet the mechanisms by which it exerts metabolic benefit remain unclear. Here, we demonstrate a model of vertical sleeve gastrectomy (VSG) in nonhuman primates (NHP) that mimics the complexity and outcomes in humans. We also show that VSG confers weight loss and durable metabolic benefit, where equivalent caloric intake in shams resulted in significant weight gain following surgery. Furthermore, we show that VSG is associated with early, weight-independent increases in bile acids, short-chain fatty acids, and reduced visceral adipose tissue (VAT) inflammation with a polarization of VAT-resident immunocytes toward highly regulatory myeloid cells and Tregs. These data demonstrate that this strongly translational NHP model can be used to interrogate factors driving successful intervention to unravel the interplay between physiologic systems and improve therapies for obesity and metabolic syndrome. [Display omitted] •A monkey model of vertical sleeve gastrectomy (VSG) accurately mimics human VSG•VSG confers durable metabolic benefits•VSG decreases crown-like structure density and alters macrophage phenotype•Interplay of metabolites and immune cell populations in VSG Immunology; Obesity medicine; Surgery
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2021.103421